The human heart delivers oxygenated blood to the organs of the body to sustain metabolism. The human heart has four chambers, two atria and two ventricles. The atria assist with filling of the ventricles, which pump blood to the body and through the lungs. The right ventricle (RV) pumps blood through the lungs to be oxygenated and the left ventricle (LV) pumps the oxygenated blood to the body.
A graph of the cardiac filling and pumping cycle and valvular events is shown in FIGS. 1a and 1b. The cardiac LV pumping cycle (LV cycle) is divided into two periods: diastole 52 and systole 54. Diastole 52 is the filling period and systole 54 is the ejection period. Five different phases of the LV cycle can be identified within the systolic and diastolic periods: isovolumic contraction 56, ejection 58, isovolumic relaxation 62, early diastolic filling (rapid filling) 64, and late diastolic filling (atrial contraction) 66. Mitral valve closure 68 (“MVC”) occurs during isovolumic contraction and aortic valve closure 72 (“AVC”) occurs during isovolumic relaxation. Also shown in the figures are the left ventricular pressure LV Press 74, a regular electrocardiogram ECG 76, the left ventricular end-diastolic volume LVEDV 78, the left ventricular end-systolic volume LVESV 82, a graph depicting heart sounds 84, the left atrial pressure LA Press 86, the aortic pressure 88, a-wave 92, c-wave 94, and v-wave 96.
Myocardial activation and systolic contraction is initiated in the atria by a regular electrical depolarization wave that spreads from the sinoatrial node to the ventricles at a normal resting cycle of 60 to 80/minute. Cardiac electrical activity can be sensed using a body surface electrocardiogram or ECG. The depolarization of the atria is sensed as a P-wave 98 on the ECG. A delay in depolarization between the atria and ventricles occurs and is measured on the ECG as the PR interval 102. Ventricular contraction and myocardial shortening starts at the interventricular septum and rapidly spreads to the posterior and lateral wall via the Purkinje system. Electrical depolarization that leads to ventricular contraction is measured on the ECG by the QRS complex 104. Following the QRS complex 104 is the T-wave 106, which reflects ventricular repolarization.
In the normal heart, a short delay from interventricular septal contraction to posterior-lateral contraction of approximately 20-40 ms occurs such that the lateral free wall is typically the first region of the heart to undergo shortening. Aortic valve closure signifies the end of the ejection phase of systole and the start of diastole. Diastole results in filling of the ventricles with blood and lengthening of the myocardium. In the normal heart diastole is typically longer than systole with the ratio dependent on heart rate.
LV myocardial motion is complex and includes both vibration and displacement (lengthening and shortening). Displacement occurs primarily along the longitudinal axis (base to apex), but there is also some radial displacement as well as clockwise and counterclockwise rotation. Displacement of the entire heart can also be caused by respiration. Superimposed on the large amplitude displacement motion is low amplitude vibrational motion related to isovolumic contraction/relaxation, valve closure, and valve pathologies such as mitral regurgitation.
The origin of LV displacement motion can be traced to the specific orientation and arrangement of muscle fibers in the myocardium. Vibrational motion of the LV is thought to be caused by acceleration and deceleration of the blood and turbulent blood flow. Studies of myocardial architecture have shown that the fibers are situated transverse and diagonal in a helical pattern. Transverse circumferential fibers are present in the base and midwall of the myocardium and produce radial narrowing of the ventricle. Systole starts with the development of tension primarily in the circumferential fibers, which stiffens and narrows the ventricle, and causes primarily radial displacement. The start of systole coincides with the isovolumic contraction phase of the LV cycle and also causes a vibrational motion thought to be related to directional changes of the blood and the accompanying acceleration/deceleration. Mitral valve closure also occurs during this isovolumic contraction period. Circumferential shortening is followed by longitudinal-diagonal fiber shortening resulting in primarily longitudinal displacement of the LV (base toward the apex) and ejection of blood. The action of these fibers also creates a rotation of the heart. This coincides with the ejection phase of the LV cycle. Mitral regurgitation is prominent during this ejection phase. Following ejection, lengthening and rotation in the opposite direction begins, and the isovolumic relaxation phase of the LV cycle occurs. Isovolumic relaxation is also thought to be associated with vibrational motion related to the acceleration/deceleration of the blood. Aortic valve closure also occurs during this phase. Early rapid filling of the LV with blood, as well as late filling, causes radial and longitudinal lengthening of the LV.
This motion of the ventricular myocardium and the LV cycle phases can be measured at the mitral annulus which is displaced radially and longitudinally. In addition, some rotation and the vibrational motion is transmitted at the annulus. Longitudinal displacement is an integral part of the global contractile function and has a good correlation with the overall ejection performance and diastolic filling performance of the ventricle.
Heart failure or cardiomyopathy is a medical syndrome characterized by deterioration of cardiac pumping performance. The primary deterioration is a progressive loss of heart muscle compliance and contractility. Loss of pump function leads to cardiac dilation, blood volume overload, pulmonary congestion, and ultimately organ failure. Symptoms of heart failure include orthopnea, dyspnea on exertion, cough, fatigue, and fluid retention. Many heart failure patients suffer from functional mitral regurgitation that can worsen with exercise and contributes to the progression of the disease. Lastly, patients with cardiomyopathy are prone to rhythm disturbances such as interventricular and intraventricular conduction delays leading to mechanical dyssynchrony, and tachyarrhythmias.
In cardiac pathology, such as heart failure, electrical conduction between atria and ventricles can be delayed excessively such that pumping function of the heart deteriorates. In addition, conduction delays in the spread of ventricular depolarization thwart the uniform spread of ventricular contraction and result in asynchronous ventricular shortening and a deterioration of performance. Some of the ventricular depolarization delays are due to abnormalities of the Purkinje system and are referred to as left or right bundle branch blocks (LBBB or RBBB). Bundle branch blocks are manifested by a wide QRS complex on the ECG.
A prolonged QRS, often manifested as an LBBB in patients with cardiomyopathy, is associated with poor prognosis. In several large clinical trials, lengthening of the QRS was independently associated with poor survival. In addition, several deleterious hemodynamic consequences arise in the presence of bundle branch block including shortening of the diastolic filling period, aggravation of mitral regurgitation, and abnormal systolic wall motion. The overall result is a typical and sometimes dramatic deterioration in cardiac performance.
Most therapies to improve cardiomyopathy are implemented and tailored empirically, or indirectly, based on patient symptoms, with little or no information on the mechanical optimization of cardiac pumping. In practice, assessment of mechanical pumping properties is difficult. Some information can be obtained by inserting catheters into the chambers of the heart, but these catheters cannot be left in chronically and it is impractical to subject patients to repeated procedures.
Objectives of cardiomyopathy therapy are to increase contractility, reduce afterload, i.e., the pressure against which the LV must pump, control blood and body water volume, blunt neurohumoral activation, improve cardiac compliance, increase ejection fraction, and reduce mitral regurgitation. Drugs, medical devices, and surgical treatments are employed to accomplish these goals and include diuretic drugs, blood pressure drugs, beta blocker drugs, cardiac pacing and resynchronization with or without tachyarrhythmia therapy, coronary artery bypass grafting, and heart transplantation.
Pacemaker therapy to treat heart failure is an established medical therapy. This therapy is employed to correct the dyssynchronous mechanical activity that occurs in heart failure by controlling the electrical activity of the heart. This form of pacing therapy is often referred to as cardiac resynchronization therapy or CRT. Dual chamber pacing (right atrium and right ventricle) to improve atrioventricular synchrony is a form of pacemaker therapy. Biventricular pacing is a newer approach that can improve cardiac function and mortality. Tachyarrhythmia and defibrillation therapy are also incorporated into the pacing therapy as heart failure patients often have problems with tachyarrhythmia. An experimental implantable pacing therapy for cardiomyopathy is cardiac contractility modulation (“CCM”) in which a voltage potential or current is applied to the myocardium during the tissue's refractory period. This current improves myocardial contractility.
CRT is achieved by pacing (inducing myocardial activation) in the RV and LV, and has assumed prominence in patients with advanced heart failure and refractory symptoms. Specific candidates include patients with a prolonged QRS duration >120 milliseconds and/or LBBB. In newer approaches the RV and LV pacing is controlled and may occur at different intervals. LV free wall pacing only is also being explored.
Most clinical trials have demonstrated that about two-thirds of patients will have a clinical response to CRT as long as optimal pharmacologic therapy is maintained. Clinical responses include improvement in New York Heart Association functional class, improved exercise capacity, a decreased need for diuretic, reduced hospitalization for heart failure management, and the like. Unfortunately, about one-third of patients do not respond, and approximately 15% of patients can actually have a worsened clinical outcome.
In biventricular pacing or CRT, cardiac leads are placed in the right atrium (RA), the RV, and LV coronary veins via the coronary sinus. The leads have electrodes that can sense cardiac electrical activity and stimulate contraction in the myocardium. The leads are connected to a hermetically sealed, battery powered, programmable pulse generator and sensor/data storage device, termed here an “IPG” that is implanted subcutaneously.
Crucial to successful CRT is deployment of the left ventricular lead. This is typically accomplished by passing the LV lead through the coronary sinus into one of its venous tributaries overlying the epicardial left ventricular surface. Conventional pacing target sites are the posterior and lateral myocardium. In principle, the target site should be the segment of latest regional myocardial contraction relative to the QRS or some other measurement of the start of ventricular contraction. Although this is predicted to be in the posterior-lateral region, the actual site tends to be rather variable and difficult to predict in the individual patient. One other criterion for employing CRT is the identification of myocardial regions that contract in the post-systolic period, or in the period after aortic valve closure. Such regions are sometimes referred to as myocardial contractility reserve, because these regions of myocardium can add or contribute to systolic ejection if they can be forced to contract during systole. Pacing of regions can induce contraction and shortening of these late-contracting regions so that they contribute to systole. Consequently, any patient with a region of myocardium that contracts and deforms in the post-systolic period are candidates for CRT, regardless of the QRS interval.
Tissue Doppler and its corresponding myocardial velocity measurement have been used to measure various mechanical properties of ventricles and atria. Characterization of systolic and diastolic function can be performed. In addition, tissue Doppler has been employed in the assessment of mitral regurgitation and ischemia.
Tissue Doppler velocity measurements can detect tissue velocity changes, but these changes do not necessarily correlate with ventricular shortening which is required for cardiac pumping during systole. In an asynchronous ventricle, contraction may not be accompanied by shortening due to the effects of earlier-contracting segments on late-contracting segments. Newer techniques that employ measurements of cardiac strain and shortening are able to assess cardiac motion.
General strategies for LV lead placement can be developed with tissue Doppler imaging, a sophisticated echocardiographic technique, which allows visualization of individual myocardial segments and their contraction patterns, and allows visualization and analysis of segmental wall motion and velocity. It has been observed that up to 50% of patients may have the left ventricular lead, when placed in a conventional fashion pacing in a zone that does not correspond to the best myocardial contraction segment, i.e. there is a mismatch between the desired target and the actual target. Moreover, it is only those patients in whom a match occurred between the paced segment and the target zone where a clinical response was observed (only in about 30-50% of patients). This may explain why there is a lower than desired clinical response rate to CRT.
To improve CRT there is not only the need to identify target zones for pacing, but also to identify suitable patients. Further, a substantial percentage of patients with a normal or only slightly-widened QRS interval may also be candidates for CRT. Tissue Doppler scans can be suitable to measure ventricular dyssynchrony and therefore may be able to identify appropriate patients and optimize therapy. One measure of dyssynchrony identified with tissue Doppler is the assessment of peak velocity delays relative to the QRS onset of different myocardial segments and the standard deviation of these delays. However, tissue Doppler imaging requires specialists to perform the scan and can only be performed during a clinical visit. Thus, continuous or daily monitoring is not possible with this technique. Moreover, the complexity of the technique makes it too cumbersome to use during the LV lead placement.
Motion of the heart and LV, both displacement and vibration, can be measured directly with an acceleration sensor. This motion can be used to characterize the LV cycle phases. Integration of the acceleration measurements during displacement provides myocardial velocity data that may closely parallel tissue Doppler imaging velocity measurements. Double mathematical integration of the acceleration sensor signal would allow characterization of the distance of displacement. Thus, an acceleration sensor-based system could be used to identify target regions of myocardium for pacing, optimize and characterize the regional and global LV response to pacing of the target region, and identify candidates for CRT, including those without a widened QRS. Since LV motion and cardiac pathologies such as mitral regurgitation occur at different frequencies, e.g., higher frequency vibration and lower frequency displacement, acceleration signals at different frequencies are ascertained. In this way, the complete LV cardiac cycle and cardiac pathologies can be characterized and monitored for changes due to pacing. An appropriately designed implantable myocardial acceleration sensing device (IAD) could monitor global and regional cardiac function long term, and would allow optimization of many treatment aspects of heart failure, including pharmacologic therapy. This monitoring may occur without the need for specialized personnel and scanning Moreover, the appropriately designed system would allow characterization of the complete cardiac cycle (systole and diastole) and global monitoring of cardiac mechanical function.
Accelerometers have been used in pacemaker IPGs for rate control purposes (U.S. Pat. Nos. 5,383,473 and 5,425,750). A sensor implanted in the heart mass for monitoring heart function by monitoring the momentum or velocity of the heart mass is generally disclosed in U.S. Pat. No. 5,454,838. A catheter for insertion into the ventricle for monitoring cardiac contractility having an acceleration transducer at or approximately at the catheter tip is generally disclosed in U.S. Pat. No. 6,077,236. Implantable leads incorporating accelerometer-based cardiac wall motion sensors and for arrhythmia discrimination are generally disclosed in U.S. Pat. Nos. 5,628,777 and 6,002,963. Accelerometers used for discrimination of various cardiac arrhythmias are also generally disclosed in U.S. Pat. No. 5,268,777. Additionally, other disclosures have proposed the use of an accelerometer to optimize pacing timing, such as AV delay/interval and interventricular (V-V) timing (U.S. Pat. Nos. 5,549,650; 6,542,775; 5,549,650, 5,540,727 and U.S. Applications 2003/0105496 A1, 2004/0172079 A1, 2004/0172078 A1, and 2005/0027320 A1).
In addition to employing sensors for monitoring therapy for cardiomyopathy, acceleration sensors have been previously disclosed for measuring the amplitude of acceleration signals during isovolumic contraction. Using a uniaxial accelerometer integrated into a right ventricular (RV) pacing lead, work done by Plicchi (“An implantable intracardiac accelerometer for monitoring myocardial contractility”, PACE 1996, 19:2066-2071) and others indicates that measurement of the peak amplitude of acceleration signals during the ICP correlates ventricular contractility and the rate of rise of ventricular pressure. Prior patent publications also disclose the measurement of peak amplitude acceleration signals to characterize contractility. For example, Chinchoy [US 2004/0172079A1 and US 2004/0172078 A1] discloses the measurement of peak amplitude of the acceleration signal during the ICP from the LV epicardium to optimize the atrioventricular (“AV”) delay and interventricular (“VV”) timing interval of a CRT device and to monitor long-term LV function. Yu and others disclose the measurement of the phase shift in the peak amplitude of acceleration signals derived from the LV and RV to optimize AV and VV interval timing of a CRT device.
Accurate measurement of the peak amplitude of an acceleration signal using an acceleration sensor as discussed in prior disclosures, may be problematic due to variables that can affect the signal. One variable is the influence of the acceleration signal related to the gravitational field of the earth. This acceleration signal will change with the angle of tilt of the sensor relative to the gravitational acceleration vector. Thus, depending on the orientation of the sensor in the heart, the acceleration signal due to earth's gravity may increase or decrease the peak amplitude. Another factor which may affect the peak amplitude is the relative motion of the lead or catheter type device to which the acceleration sensor is affixed. Relative motion of the acceleration sensor device (e.g., a catheter LV lead) in the direction of acceleration may increase the signal amplitude and, if counter to the direction of myocardial acceleration, may reduce the peak amplitude. Further, if the axis of the acceleration sensor is not parallel to the axis of motion, the amplitude of the signal will also be reduced. Lastly, the motion of the heart due to respiration may affect the accuracy of the peak amplitude.
Further in the disclosures of Chinchoy and Yu [US 2003/0104596 A1], it is not clear if the sensor is measuring vibrational or displacement motion of the heart. Measurement of these different motion types requires signal acquisition in the appropriate frequency band; however, these prior disclosures do not indicate the acquired acceleration signal's frequency band. Chinchoy indicates that the isovolumic contraction phase analyzed from the acceleration signal correlates with the S1 peak of myocardial Tissue Doppler velocity curve. However, this curve is a measurement of the displacement motion of the LV and therefore does not contain the vibrational component that may be more indicative of LV function. These above disclosures do not provide for measurement of pathologic vibrational motion, such as mitral regurgitation or the third/fourth heart sounds, and monitoring changes that may be indicative of improved LV function. Lastly, the above disclosures do not disclose a system and method for identifying target LV pacing sites for CRT through appropriate analysis of the ICP.